Multi-cohort analysis of host immune response identifies conserved protective and detrimental modules associated with severity across viruses.
conserved host response to viruses
covid-19
multi-cohort analysis
pan-virus analysis
systems immunology
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
13 04 2021
13 04 2021
Historique:
received:
23
09
2020
revised:
03
12
2020
accepted:
01
03
2021
pubmed:
26
3
2021
medline:
24
4
2021
entrez:
25
3
2021
Statut:
ppublish
Résumé
Viral infections induce a conserved host response distinct from bacterial infections. We hypothesized that the conserved response is associated with disease severity and is distinct between patients with different outcomes. To test this, we integrated 4,780 blood transcriptome profiles from patients aged 0 to 90 years infected with one of 16 viruses, including SARS-CoV-2, Ebola, chikungunya, and influenza, across 34 cohorts from 18 countries, and single-cell RNA sequencing profiles of 702,970 immune cells from 289 samples across three cohorts. Severe viral infection was associated with increased hematopoiesis, myelopoiesis, and myeloid-derived suppressor cells. We identified protective and detrimental gene modules that defined distinct trajectories associated with mild versus severe outcomes. The interferon response was decoupled from the protective host response in patients with severe outcomes. These findings were consistent, irrespective of age and virus, and provide insights to accelerate the development of diagnostics and host-directed therapies to improve global pandemic preparedness.
Identifiants
pubmed: 33765435
pii: S1074-7613(21)00114-X
doi: 10.1016/j.immuni.2021.03.002
pmc: PMC7988739
pii:
doi:
Substances chimiques
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
753-768.e5Subventions
Organisme : NIAID NIH HHS
ID : U19 AI057229
Pays : United States
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests E.J.G.B. has received honoraria from Abbott CH, Angelini Italy, bioMérieux Inc, InflaRx GmbH, MSD Greece, and XBiotech Inc.; independent educational grants from AbbVie, Abbott, Astellas Pharma Europe, AxisShield, bioMérieux Inc, InflaRx GmbH, ThermoFisher Brahms GmbH, and XBiotech Inc; and funding from the FrameWork 7 program HemoSpec (granted to the National and Kapodistrian University of Athens), the Horizon2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grant ImmunoSep (granted to the Hellenic Institute for the Study of Sepsis). P.K. is a shareholder and a consultant to Inflammatix, Inc. Y.H.B. and Y.D.H. are employees of, and stockholders in, Inflammatix, Inc.
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